The present invention pertains to a process for determining the functional residual capacity (FRC) of the lungs during respiration. The determination of the FRC during respiration therapy in general and during the diagnosis of the maturity of the lungs of respirated premature and newborn babies in particular may be helpful in the initiation and the monitoring of the necessary therapeutic measures. At the same time, disturbances in the intrapulmonary gas distribution can be quantified by such a process.
The functional residual capacity (FRC) is considered to be an important, informative variable for the respiration of a patient; however, its measurement has not yet found acceptance in routine clinical practice because of the rather complicated apparatus required. The measurement of the FRC has only been known from the area of clinical experiments so far.
The determination of the FRC can be carried out in a patient in various ways. A method known for healthy patients in the lung function laboratory is body plethysmography, in which the patient is sitting in an air-tightly closed chamber and the lung volume can be determined on the basis of the breath-dependent variations in the air pressure in the chamber. This method is very complicated and cannot be used in intensive care patients.
Another method is the so-called wash-out method. In an open breathing circuit, either the nitrogen contained in the lungs or an inert gas washed in before, usually a gas that is poorly soluble in blood, is washed out by another gas, i.e., replaced by that gas. Nitrogen wash-out methods, noble gas wash-out methods, and sulfur hexafluoride wash-out methods operate according to this principle. The FRC is calculated by measuring the amount of indicator gas washed out and its concentration in the lungs before and after the wash-out, the FRC being obtained as the quotient of the indicator gas volume washed out and the difference between the indicator gas concentration before the wash-out and the indicator gas concentration after the wash-out. The indicator gases used shall not induce any physiological, toxic or metabolic reactions in the patient""s lungs. Moreover, they shall not be possibly soluble in the blood in order not to distort the mass balance, on which the calculation of the FRC according to the wash-out method is based.
To determine the FRC by means of nitrogen wash-out, an increased oxygen concentration, e.g., 100 vol. %, is supplied for the patient for a short time or part of the nitrogen is replaced with a noble gas at constant oxygen concentration. Contrary to the nitrogen wash-out by means of noble gases, no additional gas is needed in a respirator for the nitrogen wash-out by means of an increased oxygen concentration because oxygen and normal breathing air are normally available there. However, there are reservations against increasing the oxygen concentration in the case of use for premature and newborn babies because of the suspicion that retrolental fibroplasia may develop in this case, which may subsequently lead to loss of eyesight. Conversely, the oxygen concentration cannot be reduced without problems in the case of intensive care patients, who need a high oxygen concentration, without running the risk of inadequate oxygen supply. Moreover, the measurement of the nitrogen concentration during the wash-out is technically very complicated, because nitrogen is difficult to detect. It can be carried out, e.g., with a mass spectrometer. Laughing gas, N2O, has been used as an inhalation anesthetic for a long time. Due to its light absorption behavior, it can be detected relatively rapidly and accurately by infrared optical measurement methods. It is therefore logical to use laughing gas at low concentrations as a trace gas for determining the FRC. However, laughing gas is rapidly absorbed by the blood and a considerable percentage of laughing gas, about 40%, cannot therefore be washed out directly, as a result of which the mass balance necessary for the determination of the FRC is distorted.
The wash-out method can also be carried out with so-called trace gases, e.g., noble gases, instead of nitrogen. Noble gases, e.g., helium or argon, are well suited for the determination of the FRC for physiological reasons. They are inert, they have neither toxic effect nor, at low concentrations, anesthetic effect and only insignificant quantities of these gases are dissolved in the blood. They are not combustible and are thermally stable. With such a wash-out method, the noble gas is first administered at a low concentration, e.g., 1 vol. %, during the respiration of the patient, until an equilibrium becomes established in the lung. The metering is then switched off and the noble gas is subsequently washed out with normal breathing air. The concentration and the volume flow of the expired air are now measured continuously. If noble gases are used as a trace gas, mainly mass spectrometers, which are unsuitable for routine clinical use, are likewise used for the concentration measurement.
Methane and butane may also be used as trace gases to determine the FRC. They are physiologically harmless at low concentrations and they can be readily detected according to infrared optical methods. The drawback is that methane and butane are combustible and are explosive at certain mixing ratios. An explosive mixing ratio is formed, e.g., by 4.1 vol. % of methane in usual breathing air. Contrary to the determination of the FRC in spontaneously breathing patients, a higher oxygen concentration is often necessary in intensive care patients than the concentration of about 21 vol. % normally present in the air. However, the risk of explosion also increases markedly with increasing oxygen concentration in the case of methane and butane, so that the concentration of these gases must be very low to avoid an explosive gas mixture. In light of such risks, the use of methane and butane is not indicated, especially in intensive care medicine.
As an alternative to wash-out, it is also possible to analyze the wash-in of trace gas, i.e., to set up the net balance of the trace gas flowing into the patient""s lung, by means of concentration and volume flow measurements.
To determine the FRC according to a wash-out method as well as a corresponding wash-in method, inert trace gases that are harmless for the patient are therefore sought, which can be measured with a small sensor near the patient. The sensor itself must have a very rapid time response. The response must take place in less than 25 msec in the case of the respiration of newborn babies, because a sufficient resolution of the curve showing the trace gas concentrations over time, which is necessary for the determination of the FRC according to the wash-out method, is only possible under these conditions. If the sensor is arranged in the main stream of the breathing circuit, it should be as small as possible in order not to needlessly increase the dead space, which would lead to an impairment of the quality of respiration. An increased dead space leads to the less satisfactory wash-out of carbon dioxide and therefore to hypercapnia, especially in premature and newborn babies.
Sulfur hexafluoride is mentioned as a trace gas in EP 0 653 183 B1. Sulfur hexafluoride, SF6, has been known for a long time as a trace gas for the determination of the FRC. Sulfur hexafluoride is considered to be inert and can be easily detected by means of infrared optical gas sensors; it absorbs in the wavelength range of 10.6 xcexcm.
One drawback of sulfur hexafluoride is that it can lead to very high absorption of sunlight at high altitudes of the atmosphere and thus to warming of the environment. Sulfur hexafluoride is therefore discussed in connection with the xe2x80x9cgreenhouse effect.xe2x80x9d Whenever possible, it should be replaced with more environmentally friendly gases. Moreover, a TLV (Threshold Limit Value) of 0.1 vol. % is specified for sulfur hexafluoride.
The object of the present invention is to provide a trace gas for use for determining the functional residual capacity (FRC) of the lungs of a patient or test subject, which can be detected in a simple manner, is physiologically harmless and is environmentally friendly.
According to the invention, fluoropropane is used as a trace gas for determining the functional residual capacity (FRC) of the lungs during respiration. The fluoropropane may be a heptafluoropropane, a hexafluoropropane or a perfluoropropane.
According to another aspect of the invention, a process is provided for determining the FRC, in which a breathing gas containing a predetermined concentration of fluoropropane is introduced into the lungs during a wash-in phase until the lungs become saturated with the said fluoropropane and the corresponding volumes V1, . . . , VA of the expired breathing gas are determined for consecutive breaths A=1, . . . , n during the subsequent wash-out phase, the fluoropropane concentration in the expired breathing gas is measured with a said gas sensor, and a mean expiratory fluoropropane concentration K1, . . . , KA is determined from this by a computer for each breath A=1, . . . , n. The process further comprises:
a) calculating the volume of fluoropropane having been expired until present since the beginning of the wash-out phase by the computer for each breath A=1, . . . , n as a sum of the individual volumes V1, . . . , VA of the expired breathing gas, and these volumes are multiplied by the corresponding mean fluoropropane concentration K1, . . . , KA of the fluoropropane in these volumes;
b) forming an FRCA value for the functional residual capacity (FRC) by the computer as a quotient of the expired volume of fluoropropane, which was calculated in step a), and the difference between the end tidal fluoropropane concentration K0 at the beginning of the wash-out phase and the fluoropropane concentration KA at breath A.
Steps a) and b) may be repeated until a preset number of FRCA values calculated last are within a preset tolerance range. The present tolerance range may be 5% to 20% of the FRCn value calculated last.
The use of fluoropropanes as trace gases offers a number of advantages. Fluoropropanes have been known as propellants for spray cans, where they are considered to be substitutes for the fluorochlorohydrocarbons. Moreover, fluoropropanes are readily detectable by means of infrared optical measuring instruments because they markedly absorb infrared radiation in the wavelength range between 3 and 10 xcexcm. Fluoropropanes are suitable for use as trace gases also because neither metabolic nor toxic effects on the human body are known. Their solubility in the blood is very low, and they are neither combustible nor explosive. They do not have anesthetic effect and the data currently available show that they do not pollute the environment and are not harmful for human health, either.
In a wash-out method for determining the functional residual capacity (FRC) with fluoropropane, a value is obtained for the FRC according to the formula             FRC      A        =                  1                              K            0                    -                      K            A                              ⁢              (                                            V              1                        ·                          K              1                                +          …          +                                    V              A                        ·                          K              A                                      )              ,
in which A=1, . . . , n are consecutive breaths since the beginning of the wash-out phase, V1, . . . , VA are the corresponding volumes of the expired breathing gas, and K1, . . . , KA are the fluoropropane concentrations determined for the given breath in the expired breathing gas. K0 denotes the end tidal fluoropropane concentration at the beginning of the wash-out phase, which equals, e.g., 0.8%, and Kn denotes that present at the last breath n taken into account.
In another advantageous variant of the method according to the present invention for determining the FRC, a physiologically substantiated break-off criterion is used for the measurements of the fluoropropane concentrations and the volumes in the expired breathing gas for determining the FRC, which is based directly on the convergence behavior of the values calculated for the FRC from the measured values.
If there are no disturbances in the gas distribution in the patient""s lungs, the value       FRC    1    =            1                        K          0                -                  K          1                      ·          V      1        ·          K      1      
calculated for the functional residual capacity from the first breath during a wash-out phase also corresponds essentially to the further values calculated for the FRC from a plurality of consecutive breaths during the wash-out phase.
If there are disturbances in the gas distribution in the patient""s lungs, the values       FRC    1    =            1                        K          0                -                  K          1                      ·          V      1        ·          K      1                                    xe2x80x83                ⁢                                            FRC              2                        =                                          1                                                      K                    0                                    -                                      K                    2                                                              ·                              (                                                                            V                      1                                        ·                                          K                      1                                                        +                                                            V                      2                                        ·                                          K                      2                                                                      )                                              ,                                                  xe2x80x83                ⁢                                            FRC              3                        =                                          1                                                      K                    0                                    -                                      K                    3                                                              ·                              (                                                                            V                      1                                        ·                                          K                      1                                                        +                                                            V                      2                                        ·                                          K                      2                                                        +                                                            V                      3                                        ·                                          K                      3                                                                      )                                              ,                                                  xe2x80x83                ⁢        ⋮                                          xe2x80x83                ⁢                              FRC            n                    =                                    1                                                K                  0                                -                Kn                                      ·                          (                                                                    V                    1                                    ·                                      K                    1                                                  +                …                +                                  Vn                  ·                  Kn                                            )                                          
for the functional residual capacity usually increase at the beginning and subsequently converge toward an end value. If such a convergence appears to develop, this is a meaningful break-off criterion for a method for determining the functional residual capacity (FRC) of the lungs.
The convergence of the FRC1, . . . , FRCn values can be recognized, e.g., from the fact that a preset number of FRCA values calculated last, e.g., of the three FRCnxe2x88x922, FRCnxe2x88x921 and FRCn values calculated last, is within a preset tolerance range. The tolerance range may be, e.g., 5% to 20% of the FRCn value calculated last. The FRCn value calculated last is the functional residual capacity.
On the one hand, the first breaths during the wash-out phase yield the highest concentrations and thus accurate values for the FRC because of the exponential decline of the fluoropropane concentration, and, on the other hand, precisely the first values are particularly sensitive with respect to disturbances in the gas distribution in the lungs. The evaluation of a plurality of breaths is therefore desirable in the case of disturbances in distribution. The values for the fluoropropane concentrations become very low during the breaths at the end of the wash-out phase and may already be in the range of the measuring uncertainty. Therefore, a breakdown is usually performed in practice according to certain criteria in the summation over the total amount of wash-out, e.g., when the values drop below the measuring uncertainty or after a set number of breaths.
The determination of the FRC can be initiated by the user individually or it can be preset automatically in a fixed time sequence in order to recognize, e.g., a longer trend under the effects of a respiration therapy.
Trace gas can be supplied for metering, e.g., from a, pressurized gas cylinder, in which a sufficient amount of trace gas is kept in reserve for a plurality of cycles, i.e., wash-ins. The gas heptafluoropropane has, e.g., a pressure of 2.9 bar at a temperature of 20xc2x0 C. in a pressurized gas cylinder. It is now in this liquid phase and is available for metering in the liquid or gaseous form. The pressurized gas cylinder can be plugged into an adapter provided for this purpose, as a result of which a valve is opened at the same time at the tap or a diaphragm at the tap is also pierced. The pressurized gas cylinder can be removed from the adapter in the emptied state and refilled or reused.
The present invention will be explained in greater detail below on the basis of the exemplary embodiments shown in the drawings.
The various features of novelty which characterize the invention are pointed out with particularity in the claims annexed to and forming a part of this disclosure. For a better understanding of the invention, its operating advantages and specific objects attained by its uses, reference is made to the accompanying drawings and descriptive matter in which preferred embodiments of the invention are illustrated.